Neuroendocrine Regulation of Immunity
Abstract
A reciprocal regulation exists between the central nervous and immune systems through which the CNS signals the immune system via hormonal and neuronal pathways and the immune system signals the CNS through cytokines. The primary hormonal pathway by which the CNS regulates the immune system is the hypothalamic-pituitary-adrenal axis, through the hormones of the neuroendocrine stress response. The sympathetic nervous system regulates the function of the immune system primarily via adrenergic neurotransmitters released through neuronal routes. Neuroendocrine regulation of immune function is essential for survival during stress or infection and to modulate immune responses in inflammatory disease. Glucocorticoids are the main effector end point of this neuroendocrine system and, through the glucocorticoid receptor, have multiple effects on immune cells and molecules. This review focuses on the regulation of the immune response via the neuroendocrine system. Particular details are presented on the effects of interruptions of this regulatory loop at multiple levels in predisposition and expression of immune diseases and on mechanisms of glucocorticoid effects on immune cells and molecules.
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In leukocytes, cortisol ligates cytosolic glucocorticoid receptors, and these complexes translocate to the nucleus, where they inhibit activity of several immunoregulatory transcription control pathways, including NF-κB, AP-1, and JAK-STAT factors.
“In leukocytes, cortisol ligates cytosolic glucorticoid receptors (GR), and these complexes translocate to the nucleus, where they inhibit activity of several immunoregulatory transcription control pathways, including nuclear-factor kappa-B (NF-κB), activator-protein 1 (AP-1), and JAK-STAT factors (10).”
From A Functional Genomic Fingerprint of Chronic Stress in Humans: Blunted Glucocorticoid and Increased NF-κB Signaling (2008) · cites this paper as [10]
ACTH acts on the adrenal cortex to stimulate glucocorticoid synthesis and release.
“Subsequently, ACTH acts on the adrenal cortex to stimulate the synthesis and release of glucocorticoids (Fig 1A)6.”
From Corticosteroids (2016) · cites this paper as [6]
CRH and AVP act on the anterior pituitary to activate corticotroph cells to secrete ACTH into the general circulation.
“These hormones act on the anterior pituitary where they activate corticotroph cells to secrete adrenocorticotrophin hormone (ACTH) into the general circulation.”
From Corticosteroids (2016) · cites this paper as [6]
Inputs from the suprachiasmatic nucleus stimulate the paraventricular nucleus of the hypothalamus to release CRH and AVP.
“Inputs from the suprachiasmatic nucleus (SCN) stimulate the para-ventricular nucleus (PVN) of the hypothalamus to release corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP).”
From Corticosteroids (2016) · cites this paper as [6]
The circadian release of glucocorticoids from the adrenal glands is controlled by the hypothalamic-pituitary-adrenal axis.
“The circadian profile of glucocorticoid release from the adrenal glands is regulated by the hypothalamic-pituitary-adrenal (HPA) axis.”
From Corticosteroids (2016) · cites this paper as [6]
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“The timely regulation of this immune continuum is mediated by intertwined immune, endocrine, and neural regulatory pathways that safeguard against undue tissue and cell damage [6,7].”
Background
- Authors
- Webster, J. I., Tonelli, L., & Sternberg, E. M.
- Affiliations
- National Institute of Mental Health (US)
- ORCID
- Tonelli, Leonardo
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 2002-04
- Volume
- 20
- Issue
- 1
- Pages
- 125-163
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- OpenAlex
- W2119573232
- Cited by
- 957
- References
- 13
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 25 · 2023: 23 · 2022: 41 · 2021: 35 · 2020: 35 · 2019: 29 · 2018: 31 · 2017: 31 · 2016: 37 · 2015: 44 · 2014: 49 · 2013: 48 · 2012: 54
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
- Keywords
- neuroendocrine-immune regulation, hypothalamic-pituitary-adrenal axis, neuroendocrine stress response, glucocorticoids, glucocorticoid receptor, sympathetic nervous system, adrenergic neurotransmitters, cytokines, central nervous system-immune system interaction, immune disorders, inflammatory diseases
- MeSH terms
- Animals, Glucocorticoids, Humans, Lymphocytes, Neurosecretory Systems, Receptors, Glucocorticoid, Neuroimmunomodulation, Cell Adhesion Molecules, Cytokines, Models, Immunological, Inflammation Mediators
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